This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The overall goal of this project is to identify strategies by which the immunogenicity of AIDS vaccines that are derived from Modified Vaccinia Ankara (MVA)-based viral vectors can be significantly augmented. In this project, we have developed and characterized an MVA-based HIV vaccine, from which several endogenous poxvirus immune-evasion genes have been deleted, that expresses consensus HIV subtype C Gag and Env antigens. This vaccine has been shown to elicit significantly higher levels of HIV-specific CD8 and CD4 T cell responses, as well as HIV envelope-specific antibody responses, as compared to the parental control vector, in MHC-disparate populations of rhesus macaques. Presently ongoing studies with this vaccine include a preclinical trial in rhesus macaques that is designed to test the hypothesis that the immunogenicity of this improved vector may be even further augmented through co-administration with specific toll-like receptor (TLR) -7, and -9 agonists. In addition, analogous recombinant MVA vectors expressing SIV, rather than HIV, antigens are currently being assessed in rhesus macaques for their ability to elicit systemic and mucosal immune responses, as well as protection against mucosal SIVmac239 challenge, following both homologous prime-boost immunization regimens and heterologous prime-boost immunizations with adenoviral vectors. Particularly, in light of recent positive results from the HIV vaccine efficacy trial in Thailand (RV144), the development of highly immunogenic AIDS vaccines from poxvirus vectors remains a high priority for the field.